ABSTRACT
BACKGROUND: The mean platelet volume/platelet count ratio (MPV/PC) ratio based on the preoperative peripheral MPV and PCcan be used to predict the prognosis of multiple malignant tumors. OBJECTIVE: To evaluate the prognostic value of MPV/PC in cervical cancer patients. METHODS: This study enrolled 408 patients who had undergone radical surgery for cervical cancer and evaluated the correlation of MPV/PC with patient prognosis in the primary cohort and validation cohort. Additionally, independent prognostic factors were incorporated to construct the prognostic nomogram, and the area under the receiver operating characteristic (ROC) curve (AUC) value was calculated to analyze the prognostic predictive ability of the nomogram. RESULTS: In the primary cohort, Kaplan-Meier survival analysis indicated that the overall survival (OS) for patients with MPV/PC ≤ 0.41 was significantly lower than that in patients with MPV/PC > 0.41. MPV/PC was an independent prognostic factor for resectable cervical cancer patients. Compared with neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) or monocyte/lymphocyte ratio (MLR), the AUC values of MPV/PC in predicting the 3- and 5-year survival rates for cervical cancer patients were greater. Similar results were verified in the validation cohort. Subsequently, the nomogram constructed based on MPV/PC, International Federation of Gynecology and Obstetrics (FIGO) classification and lymphovascular invasion performed well to accurately predict the prognosis of cervical cancer patients. The 3- and 5-year survival rates predicted by the nomogram were highly consistent with the real observations. Similar results were also displayed in the validation cohort. CONCLUSIONS: MPV/PC may be used as a novel independent prognostic factor for patients with resectable cervical cancer. Compared with the FIGO classification system, the nomogram integrating MPV/PC maybe reliably predict the survival of cervical cancer patients after radical surgery.
Subject(s)
Mean Platelet Volume , Platelet Count , Uterine Cervical Neoplasms/blood , Uterine Cervical Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Leukocyte Count , Lymphocytes , Middle Aged , Monocytes , Neutrophils , Nomograms , Preoperative Period , Prognosis , ROC Curve , Survival Rate , Uterine Cervical Neoplasms/pathology , Young AdultABSTRACT
BACKGROUND: To establish a novel delivery system of RGD-conjugated resveratrol human serum albumin (HAS) nanoparticles in ovarian cancer therapy. METHODS: The nanoparticles system was characterized for physicochemical properties, the stability in the serum and in vitro release. The comparison between RVT injection, HSA-RVT NPs and RGD-HSA-RVT NPs regarding tissue distributions and pharmacokinetics was also carried out using mice as the animal models. RESULTS: The results showed that RGD-HSA-RVT NPs were characterized of small particle size about 128.2 nm and negative zeta potential about -21.42 mV, and drug controlled to release slowly on a biphasic pattern. Compared with control groups, RGD-HSA-RVT NPs showed the higher cellular uptake and cell inhibition rates. In vivo data showed that RGD-HSA-RVT NPs have good tumor enrichment characteristics and a significant difference in tumor inhibition, compared with the control group. CONCLUSION: RGD-conjugated resveratrol HSA nanoparticles are an ideal drug delivery system, which can play a role in the treatment of ovarian cancer.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Delivery Systems , Nanoparticles/chemistry , Oligopeptides/pharmacology , Ovarian Neoplasms/drug therapy , Resveratrol/pharmacology , Serum Albumin, Human/chemistry , Animals , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Carriers/chemistry , Drug Screening Assays, Antitumor , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Oligopeptides/chemistry , Ovarian Neoplasms/pathology , Resveratrol/chemistryABSTRACT
Ovarian cancer is one of the most lethal malignant gynecologic tumors with a high relapse rate worldwide. Cancer stem cells (CSCs) have been identified in ovarian cancer and other malignant tumors as a small population of cells that are capable of self-renewal and multidifferentiation. CD133+ ovarian CSCs have been reported to be more tumorigenic and more resistant to chemotherapeutic treatment. Thus, CD133 has emerged as one of the most promising therapeutic markers for ovarian cancer treatment. In the current study, we constructed a recombinant adenovirus Cre/loxP regulation system to selectively introduce truncated Bid (tBid) expression specifically targeting CD133+ in ovarian CSCs. The results demonstrated that the coinfection of Ad-CD133-Cre and Ad-CMV-LoxP-Neo-LoxP-tBid significantly increased tBid expression in CD133+ ovarian CSCs. Moreover, the tBid overexpression induced by a recombinant adenovirus Cre/loxP system dramatically inhibited cell proliferation and invasion, significantly elevated cell apoptosis, and activated the mitochondrial apoptosis pathway in CD133+ ovarian CSCs. Additionally, recombinant adenovirus Cre/loxP system-mediated tBid overexpression suppressed the tumorigenic potential of CD133+ ovarian CSCs in a xenograft mouse model. In conclusion, our study successfully constructed a recombinant adenovirus Cre/loxP system and induced tBid overexpression in CD133+ ovarian CSCs, providing a new therapeutic approach for ovarian cancer treatment.
Subject(s)
AC133 Antigen/metabolism , BH3 Interacting Domain Death Agonist Protein/genetics , Cell Transformation, Neoplastic/genetics , Neoplastic Stem Cells/metabolism , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Adenoviridae/genetics , Animals , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation , Disease Models, Animal , Female , Gene Expression , Gene Expression Regulation, Neoplastic , Genetic Vectors/genetics , Homologous Recombination , Humans , Mice , Mitochondria/genetics , Mitochondria/metabolism , Ovarian Neoplasms/pathology , Sequence Deletion , Transduction, Genetic , Xenograft Model Antitumor AssaysABSTRACT
Cancer stem cells are a small subset of cancer cells that contribute to cancer progression, metastasis, chemoresistance and recurrence. CD133-positive (CD133+) ovarian cancer cells have been identified as ovarian cancer stem cells. Adenovirus-mediated gene therapy is an innovative therapeutic method for cancer treatment. In the present study, we aimed to develop a new gene therapy to specifically eliminate CD133+ ovarian cancer stem cells by targeting CD133. We used the Cre/LoxP system to augment the selective expression of the truncated Bid (tBid) gene as suicide gene therapy in CD133+ ovarian cancer stem cells. The adenovirus (Ad)-CD133-Cre expressing Cre recombinase under the control of the CD133 promoter and Ad-CMV-LoxP-Neo-LoxP-tBid expressing tBid under the control of the CMV promoter were successfully constructed using the Cre/LoxP switching system. The co-infection of Ad-CMV-LoxP-Neo-LoxP-tBid and Ad-CD133-Cre selectively induced tBid overexpression, which inhibited cell growth and triggered the cell apoptosis of CD133+ ovarian cancer stem cells. The Cre/LoxP system-mediated tBid overexpression activated the pro-apoptotic signaling pathway and augmented the cytotoxic effect of cisplatin in CD133+ ovarian cancer stem cells. Furthermore, in xenograft experiments, co-infection with the two recombinant adenoviruses markedly suppressed tumor growth in vivo and promoted cell apoptosis in tumor tissues. Taken together, the present study provides evidence that the adenovirus-mediated tBid overexpression induced by the Cre/LoxP system can effectively eliminate CD133+ ovarian cancer stem cells, representing a novel therapeutic strategy for the treatment of ovarian cancer.
Subject(s)
Adenoviridae/genetics , Apoptosis/genetics , BH3 Interacting Domain Death Agonist Protein/genetics , Genetic Therapy/methods , Integrases/genetics , Neoplastic Stem Cells/physiology , Ovarian Neoplasms/therapy , AC133 Antigen/metabolism , Animals , BH3 Interacting Domain Death Agonist Protein/chemistry , Codon, Nonsense , Female , Gene Expression Regulation, Neoplastic , Gene Transfer Techniques , Genetic Vectors , HEK293 Cells , Humans , Mice , Mice, SCID , Mutagenesis, Site-Directed , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
The expression of KiSS-1, MMP-9 and MMP-2 mRNAs and proteins was studied in placentas of women with preeclampsia (PE, n=47) and women of normal pregnancy (NP; n=30). In addition, KiSS-1 mRNA expression as well as cell growth, proliferation and invasion were examined in JAR cells (human trophoblast cell line) transfected with pcDNA3-KiSS-1vector. Expression of KiSS-1 mRNA and protein was higher (p<0.05) in women with PE compared with that of NP women. In contrast, expression of MMP-9 and MMP-2 was lower (p<0.05) in PE than in NP women. KiSS-1 mRNA was detected in JAR cells successfully transfected with pcDNA3-KiSS-1 gene (JAR-K1, JAR-K2, JAR-K3). KiSS-1 mRNA was not detected in JAR cells transfected with pcDNA3 gene (JAR-P1, JAR-P2) and non-transfected JAR cells. No difference (p>0.05) was observed in cell growth among these three cell types. Invasion ability was significantly lower (p<0.01) in JAR-K1, JAR-K2 and JAR-K3 cells compared to JAR-P cells and non-transfected JAR cells. Overexpression of KiSS-1 and insufficient expression of MMP-9 and MMP-2 in placenta were demonstrated in women with PE. The data suggests that KiSS-1 gene plays an important role in inhibiting trophoblast invasion during placental development.
